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CompletedNCT03952039FREEDOM2Updated Aug 28, 2025Results posted

An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

A Phase 3 interventional study of FEDRATINIB and Best Available Therapy (BAT) in Primary Myelofibrosis, Post-Polycythemia Vera and Myelofibrosis, sponsored by Celgene. Completed at 107 sites in 16 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-28.

Sponsored by Celgene · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
202
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.

Read the detailed description

This Phase 3, multicenter, randomized, two-arm, open-label study will include subjects with intermediate or high-risk (as per the DIPSS score) primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF). This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical Practices (GCPs).

Study design includes:

  • A 28-day Screening Period
  • 2:1 Randomization to fedratinib or best available therapy (BAT)

  • Stratification at Randomization according to:

    • Spleen size by palpation: \< 15 cm below left costal margin (LCM) versus ≥ 15 cm below LCM
    • Platelets ≥ 50 to \< 100 x 109/L versus platelets ≥ 100 x 109/L
    • Refractory or relapsed to ruxolitinib treatment versus intolerant to ruxolitinib treatment
  • Study Treatment Period (time on study drug plus 30 days after last dose)
  • Subjects are allowed to crossover from BAT to the fedratinib arm after the Cycle 6 response assessment or before the Cycle 6 response assessment in the event of a confirmed progression of splenomegaly by MRI/CT scan
  • A Survival Follow-up Period for progression and survival
02

Conditions studied

  • Primary Myelofibrosis
  • Post-Polycythemia Vera
  • Myelofibrosis

Keywords

  • MF
  • myeloproliferative neoplasms
  • MPN
  • myelofibrosis
  • PMF
  • post-PV
  • Post-Polycythemia Vera
  • post-ET MF
  • Post-Essential Thrombocythemia Myelofibrosis
03

In context

Primary Myelofibrosis

419 studies on the registry are indexed under Primary Myelofibrosis; 117 are open to participants now.

This study's enrollment of 202 is above the median of 44 across 347 interventional studies indexed under Primary Myelofibrosis.

Browse Primary Myelofibrosis studies →

Lead sponsor

Celgene is the lead sponsor of 419 studies on the registry; 13 are open to participants now.

Of its 100 completed or terminated interventional studies of FDA-regulated products, 29 (29%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Subject is at least 18 years of age at the time of signing the informed consent form (ICF)
  2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2
  3. Subject has diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-ET or post-PV myelofibrosis according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology report
  4. Subject has a DIPSS Risk score of Intermediate-2 or High
  5. Subject has a measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥ 450 cm3 by MRI or CT-scan and by palpable spleen measuring ≥ 5 cm below the left costal margin
  6. Subject has a measurable total symptoms score (≥ 1) as measured by the Myelofibrosis Symptom Assessment Form (MFSAF)

  7. Subject has been previously exposed to ruxolitinib, and must meet at least one of the following criteria (a and/or b)

    1. Treatment with ruxolitinib for ≥ 3 months with inadequate efficacy response (refractory) defined as \< 10% spleen volume reduction by MRI or \< 30% decrease from baseline in spleen size by palpation or regrowth (relapsed) to these parameters following an initial response

    2. Treatment with ruxolitinib for ≥ 28 days complicated by any of the following (intolerant):

      • Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) or
      • Grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with ruxolitinib
  8. Subject must have treatment-related toxicities from prior therapy resolved to Grade 1 or pretreatment baseline before start of last therapy prior to randomization
  9. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
  10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements

  11. A female of childbearing potential (FCBP) must:

    1. Have 2 negative pregnancy tests as verified by the Investigator during screening prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
    2. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use and be able to comply with highly effective contraception without interruption, -14 days prior to starting investigational product, during the study treatment (including dose interruptions), and for 30 days after discontinuation of study treatment.

    Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).

  12. A male subject must:

Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 30 days following investigational product discontinuation, or longer if required for each compound and/or by local regulations, even if he has undergone a successful vasectomy

Exclusion criteria

Exclusion Criteria:

  1. Any of the following laboratory abnormalities:

    1. Platelets \< 50 x 109/L
    2. Absolute neutrophil count (ANC) \< 1.0 x 109/L
    3. White blood count (WBC) > 100 x 109/L
    4. Myeloblasts ≥ 5 % in peripheral blood
    5. Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (as per the Modification of Diet in Renal Disease [MDRD] formula)
    6. Serum amylase or lipase > 1.5 x upper limit of normal (ULN)
    7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    8. Total bilirubin > 1.5 x ULN, subject's total bilirubin between 1.5 - 3.0 x ULN are eligible if the direct bilirubin fraction is \< 25% of the total bilirubin
  2. Subject is pregnant or lactating female
  3. Subject with previous splenectomy
  4. Subject with previous or planned hematopoietic cell transplant
  5. Subject with prior history of encephalopathy, including Wernicke's (WE)
  6. Subject with signs or symptoms of encephalopathy, including WE (eg, severe ataxia, ocular paralysis or cerebellar signs)
  7. Subject with thiamine deficiency, defined as thiamine levels in whole blood below normal range according to the central laboratory and not demonstrated to be corrected prior to randomization
  8. Subject with concomitant treatment with or use of pharmaceutical, herbal agents or food known to be strong or moderate inducers of Cytochrome P450 3A4 (CYP3A4), or dual CYP2C19 and CYP3A4 inhibitors
  9. Subject on any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), anagrelide, immunosuppressive therapy, systemic corticosteroids > 10 mg/day prednisone or equivalent. Subjects who have had prior exposure to hydroxyurea (eg, Hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to randomization
  10. Subject has received ruxolitinib within 14 days prior to randomization
  11. Subject with previous exposure to Janus kinase (JAK) inhibitor(s) other than ruxolitinib treatment
  12. Subject on treatment with aspirin with doses > 150 mg daily
  13. Subject with major surgery within 28 days prior to randomization
  14. Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, non-alcoholic steatohepatitis)
  15. Subject with prior malignancy other than the disease under study unless the subject has not required treatment for the malignancy for at least 3 years prior to randomization. However, subject with the following history/concurrent conditions provided successfully treated may enroll: non-invasive skin cancer, in situ cervical cancer, carcinoma in situ of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system), or is free of disease and on hormonal treatment only
  16. Subject with uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4)
  17. Subject with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC)
  18. Subject with serious active infection
  19. Subject with presence of any significant gastric or other disorder that would inhibit absorption of oral medication
  20. Subject is unable to swallow capsule
  21. Subject with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
  22. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
  23. Subject has any condition that confounds the ability to interpret data from the study
  24. Subject with participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to randomization
  25. Subject with a life expectancy of less than 6 months
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
202 participants (actual)

Study arms

  • Experimental
    Fedratinib 400mg/day

    Will include up to 128 subjects receiving fedratinib 400 mg self-administered Investigational Product (IP) on an outpatient basis, once daily preferably together with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.

    Drug: FEDRATINIB

  • Active comparator
    Best Available Therapy (BAT)

    Best-available Investigator-selected therapy included a number of available compounds to treat MF and/or its symptoms and was chosen by the investigator for each subject. Therapy changed at different times during the treatment period. No investigational agents (e.g. not approved for the treatment of any indication) were allowed. BAT also included the choice of no treatment.

    Drug: Best Available Therapy (BAT)

Interventions

  • DrugFEDRATINIB

    A potent and selective inhibitor of JAK2 kinase activity

  • DrugBest Available Therapy (BAT)

    Best available therapy (BAT)

06

What researchers measure

Primary outcomes

  1. Spleen Volume Response Rate (RR)

    Percentage of participants who have ≥ 35% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

    Time frame: From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

Secondary outcomes

  1. Symptom Response Rate (SRR)

    Percentage of participants with ≥ 50% reduction in total symptom scores measured by Myelofibrosis Symptom Assessment Form (MFSAF) 4.0 at end of cycle 6. Subjects with a missing TSS at the end of cycle 6 or who had disease progression before the end of the cycle 6 will be considered non-responders. MFSAF measures the sum of 7 symptoms on a scale from 0 to 10 (0 being absent and 10 being the worst imagineable). The lower the score the better. A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The SRRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in SRRs and 95% confidence interval of the difference for fedratinib to BAT.

    Time frame: From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

  2. Spleen Volume Response Rate (RR25)

    Percentage of participants who have ≥ 25% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

    Time frame: From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

  3. Number of Participants With All Grade Treatment Emergent Adverse Events (AEs) and Grade 3 to 4 Treatment Emergent AEs

    Number of participants with all grade adverse events (AEs) and grade 3 to 4 AEs

    Time frame: From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

  4. Number of Participants With Hematology Laboratory Abnormalities

    Number of participants with hematology laboratory abnormalities in the following parameters: hemoglobin (decreased), leukocytes (increase and decrease), lymphocytes (decreased), neutrophils (segmented and band form decreased), Platelets (decreased).

    Time frame: From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

  5. Spleen Response Rate by Palpation (RRP)

    Spleen response rate by palpation is the percentage of participants at the end of cycle 6 with a spleen response according to the IWG-MRT 2013 criteria. A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable\*\* or A baseline splenomegaly that is palpable at \> 10 cm, below the LCM, decreases by ≥ 50%\*\* Participants with a missing spleen size assessment at the end of cycle 6 including those who meet the criteria for progression of splenomegaly before end of cycle 6 will be considered not to be responders.

    Time frame: From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

  6. Durability of Spleen Volume Response (DR)

    Durability of spleen volume response (DR) by MRI/CT is defined as the date from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) in spleen volume per the IWG-MRT 2013 criteria or death, whichever is earlier. In the absence of an event before the analysis is performed, the DR will be censored at the date of the last valid assessment performed before the analysis performed date.

    Time frame: From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

  7. Durability of Spleen Response by Palpation (DRP)

    Durability of spleen response by palpation (DRP) is defined as time from the date of the first documented palpable spleen response, according to the IWG-MRT 2013 to the date of the subsequent PD in spleen size according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date.

    Time frame: From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

  8. Durability of Symptoms Response (DSR)

    The DSR is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction \< 50%. In the absence of TSS reduction \< 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

    Time frame: From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

  9. Assessment of the Effectiveness of Risk Mitigation Strategy for ≥3 Grade Gastrointestinal Adverse Events and Any Grade Wernickes Encephalopathy

    Number of participants with a CTCAE Grade ≥3 of nausea, diarrhea, or vomiting and any grade wernickes encephalopathy.

    Time frame: From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

  10. Number of Participants With Thiamine Levels Below the Lower Limit of Normal

    Number of participants with thiamine levels below the lower limit of normal

    Time frame: From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

  11. Mean Change in EORTC QOL-C30 at Cycle 7 Day 1 as Compared With Baseline

    QLQ-C30 - The EORTC QLQ-C30 was developed to assess the quality of life of cancer patients. It consists of 30 items classified into 15 domains including 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); a global QOL subscale; and 6 single items addressing various symptoms and perceived financial impact. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions.

    Time frame: from the start of cycle 1 to cycle 7 day 1 approximately 170 days.

  12. Mean Change From Baseline in EQ-5D-5L Utility Index Score

    EQ-5D-5L - The EQ-5D-5L is a generic, self-administered preference-based measure of health. The five dimensions covered by the EQ-5D-5L include mobility, self-care, pain, usual activities, and anxiety/depression and is converted into a single summary index that can range from -0.594 to 1.0, with a score of 0 indicating death, 1.00 indicating "full health," and negative scores reflecting states perceived to be worse than death. Respondent's self-rated health on a vertical, 0 to 100 scale where 100 = "Best imaginable health state" and 0 = "Worst imaginable health state"

    Time frame: from the start of cycle 1 to cycle 7 day 1 approximately 170 days.

  13. Time to Spleen and Disease Progression Free Survival (SDPFS)

    Time from randomization to death due to any reason or disease progression (modified IWG-MRT 2013 including ≥ 25% increase in spleen volume by MRI/CT).

    Time frame: From randomization to the End of Survival Follow-up

  14. Overall Survival

    Time from randomization to death due to any reason

    Time frame: From Randomization to the end of Survival Follow Up

07

Results

Posted Jan 30, 2024

Participant flow

Participant flow — Overall Study
MilestoneFedratinibBest Available Therapy (BAT)
Started13467
Participants who crossed over046
Completed4328
Not completed9139
Withdrew: Adverse event228
Withdrew: Withdrawal by participant1712
Withdrew: Death136
Withdrew: Lack of efficacy122
Withdrew: Physician decision93
Withdrew: Progressive disease64
Withdrew: Other reasons124

Outcome measures

PrimarySpleen Volume Response Rate (RR)

Percentage of participants who have ≥ 35% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

Time frame:
From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days
Reported as:
Number · Percentage of Participants
Spleen Volume Response Rate (RR)
Percentage of ParticipantsFedratinibBest Available Therapy (BAT)
Spleen Volume Response Rate (RR)35.8 (27.7 to 44.6)6.0 (1.7 to 14.6)
Statistical analysis
  • Fedratinib vs Best Available Therapy (BAT) · Cochran-Mantel-Haenszel · p = <0.0001 · Difference in proportion: 29.6 · 95% CI 19.9 to 39.4Cochran-Mantel-Haenszel test using the Greenland and Robins method to adjust for stratification factors: spleen size by palpation and platelet counts.
SecondarySymptom Response Rate (SRR)

Percentage of participants with ≥ 50% reduction in total symptom scores measured by Myelofibrosis Symptom Assessment Form (MFSAF) 4.0 at end of cycle 6. Subjects with a missing TSS at the end of cycle 6 or who had disease progression before the end of the cycle 6 will be considered non-responders. MFSAF measures the sum of 7 symptoms on a scale from 0 to 10 (0 being absent and 10 being the worst imagineable). The lower the score the better. A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The SRRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in SRRs and 95% confidence interval of the difference for fedratinib to BAT.

Time frame:
From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days
Reported as:
Number · Percentage of Participants
Symptom Response Rate (SRR)
Percentage of ParticipantsFedratinibBest Available Therapy (BAT)
Symptom Response Rate (SRR)34.1 (25.9 to 43.1)16.9 (8.8 to 28.3)
Statistical analysis
  • Fedratinib vs Best Available Therapy (BAT) · Cochran-Mantel-Haenszel · p = 0.0033 · Difference in proportion: 17.1 · 95% CI 4.8 to 29.4CMH test using the Greenland and Robins method to adjust for stratification factors: spleen size by palpation and platelet counts.
SecondarySpleen Volume Response Rate (RR25)

Percentage of participants who have ≥ 25% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

Time frame:
From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days
Reported as:
Number · Percentage of Participants
Spleen Volume Response Rate (RR25)
Percentage of ParticipantsFedratinibBest Available Therapy (BAT)
Spleen Volume Response Rate (RR25)47.0 (38.3 to 55.8)13.4 (6.3 to 24.0)
Statistical analysis
  • Fedratinib vs Best Available Therapy (BAT) · Cochran-Mantel-Haenszel · p = <0.0001 · Difference in proportion: 33.5 · 95% CI 21.9 to 45.1Cochran-Mantel-Haenszel test using the Greenland and Robins method to adjust for stratification factors: spleen size by palpation and platelet counts.
SecondaryNumber of Participants With All Grade Treatment Emergent Adverse Events (AEs) and Grade 3 to 4 Treatment Emergent AEs

Number of participants with all grade adverse events (AEs) and grade 3 to 4 AEs

Time frame:
From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days
Reported as:
Count of participants · Participants
Number of Participants With All Grade Treatment Emergent Adverse Events (AEs) and Grade 3 to 4 Treatment Emergent AEs
ParticipantsFedratinibBest Available Therapy (BAT)
All Grade AEs13265
Grade 3 and 4 AEs8829
SecondaryNumber of Participants With Hematology Laboratory Abnormalities

Number of participants with hematology laboratory abnormalities in the following parameters: hemoglobin (decreased), leukocytes (increase and decrease), lymphocytes (decreased), neutrophils (segmented and band form decreased), Platelets (decreased).

Time frame:
From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days
Reported as:
Count of participants · Participants
Number of Participants With Hematology Laboratory Abnormalities
ParticipantsFedratinibBest Available Therapy (BAT)
Hemoglobin Decreased All Grades12964
Hemoglobin Decreased Grade 36220
Hemoglobin Decreased Grade 400
Leukocytes Decreased All Grades4119
Leukocytes Decreased Grade 383
Leukocytes Decreased Grade 410
Leukocytes Increased All Grades44
Leukocytes Increased Grade 344
Leukocytes Increased Grade 400
Lymphocytes Decreased All Grades4920
Lymphocytes Decreased Grade 3207
Lymphocytes Decreased Grade 410
Neutrophils, segmented and band from decreased All Grades3415
Neutrophils, segmented and band from decreased Grade 3114
Neutrophils, segmented and band from decreased Grade 400
Platelets Decreased All Grades7343
Platelets Decreased Grade 32410
Platelets Decreased Grade 432
SecondarySpleen Response Rate by Palpation (RRP)

Spleen response rate by palpation is the percentage of participants at the end of cycle 6 with a spleen response according to the IWG-MRT 2013 criteria. A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable\*\* or A baseline splenomegaly that is palpable at \> 10 cm, below the LCM, decreases by ≥ 50%\*\* Participants with a missing spleen size assessment at the end of cycle 6 including those who meet the criteria for progression of splenomegaly before end of cycle 6 will be considered not to be responders.

Time frame:
From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days
Reported as:
Number · Percentage of Participants
Spleen Response Rate by Palpation (RRP)
Percentage of ParticipantsFedratinibBest Available Therapy (BAT)
Spleen Response Rate by Palpation (RRP)28.4 (20.9 to 36.8)7.7 (2.5 to 17.0)
Statistical analysis
  • Fedratinib vs Best Available Therapy (BAT) · Greenland and Robins method · Greenland and robins method: 19.9 · 95% CI 10.0 to 29.7
SecondaryDurability of Spleen Volume Response (DR)

Durability of spleen volume response (DR) by MRI/CT is defined as the date from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) in spleen volume per the IWG-MRT 2013 criteria or death, whichever is earlier. In the absence of an event before the analysis is performed, the DR will be censored at the date of the last valid assessment performed before the analysis performed date.

Time frame:
From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.
Reported as:
Median · Weeks
Durability of Spleen Volume Response (DR)
WeeksFedratinibBest Available Therapy (BAT)
Durability of Spleen Volume Response (DR)86.3 (63.0 to 126.4)NA (NA to NA)
SecondaryDurability of Spleen Response by Palpation (DRP)

Durability of spleen response by palpation (DRP) is defined as time from the date of the first documented palpable spleen response, according to the IWG-MRT 2013 to the date of the subsequent PD in spleen size according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date.

Time frame:
From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.
Reported as:
Median · Weeks
Durability of Spleen Response by Palpation (DRP)
WeeksFedratinibBest Available Therapy (BAT)
Durability of Spleen Response by Palpation (DRP)118.3 (76.0 to NA)47.1 (21.7 to NA)
SecondaryDurability of Symptoms Response (DSR)

The DSR is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction \< 50%. In the absence of TSS reduction \< 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

Time frame:
From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.
Reported as:
Median · Weeks
Durability of Symptoms Response (DSR)
WeeksFedratinibBest Available Therapy (BAT)
Durability of Symptoms Response (DSR)12.1 (8.1 to 16.1)10.1 (4.1 to 16.7)
SecondaryAssessment of the Effectiveness of Risk Mitigation Strategy for ≥3 Grade Gastrointestinal Adverse Events and Any Grade Wernickes Encephalopathy

Number of participants with a CTCAE Grade ≥3 of nausea, diarrhea, or vomiting and any grade wernickes encephalopathy.

Time frame:
From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days
Reported as:
Count of participants · Participants
Assessment of the Effectiveness of Risk Mitigation Strategy for ≥3 Grade Gastrointestinal Adverse Events and Any Grade Wernickes Encephalopathy
ParticipantsFedratinibBest Available Therapy (BAT)
≥3 grade Diarrhea20
≥3 grade Nausea10
≥3 grade Vomitting00
Any Grade Wernickes Encephalopathy10
SecondaryNumber of Participants With Thiamine Levels Below the Lower Limit of Normal

Number of participants with thiamine levels below the lower limit of normal

Time frame:
From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days
Reported as:
Count of participants · Participants
Number of Participants With Thiamine Levels Below the Lower Limit of Normal
ParticipantsFedratinibBest Available Therapy (BAT)
Cycle 130
Cycle 2130
Cycle 3111
Cycle 410
Cycle 510
Cycle 621
SecondaryMean Change in EORTC QOL-C30 at Cycle 7 Day 1 as Compared With Baseline

QLQ-C30 - The EORTC QLQ-C30 was developed to assess the quality of life of cancer patients. It consists of 30 items classified into 15 domains including 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); a global QOL subscale; and 6 single items addressing various symptoms and perceived financial impact. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions.

Time frame:
from the start of cycle 1 to cycle 7 day 1 approximately 170 days.
Reported as:
Mean · Scores on a Scale
Mean Change in EORTC QOL-C30 at Cycle 7 Day 1 as Compared With Baseline
Scores on a ScaleFedratinibBest Available Therapy (BAT)
Global Heath Status10.3 ± 27.4213.1 ± 26.16
Physical Functioning8.2 ± 19.5711.1 ± 26.61
Role Functioning8.1 ± 34.2612.7 ± 40.79
Emotional Functioning7.0 ± 19.635.6 ± 25.86
Cognitivie Functioning1.7 ± 19.835.6 ± 17.74
Social Functioning6.5 ± 29.180.0 ± 27.89
Fatigue-15.2 ± 29.34-16.4 ± 33.81
Nausea and Vomitting-1.7 ± 15.32-9.5 ± 28.17
Pain-12.9 ± 25.88-9.5 ± 33.57
Dyspnea-9.0 ± 31.04-22.2 ± 35.49
Insomnia-11.4 ± 30.50-7.9 ± 25.61
Appetite Loss-19.5 ± 32.84-20.6 ± 35.71
Constipation-0.5 ± 31.34-9.5 ± 35.19
Diarrhea5.3 ± 27.196.3 ± 17.06
Financial Difficulties3.9 ± 21.031.6 ± 12.81
SecondaryMean Change From Baseline in EQ-5D-5L Utility Index Score

EQ-5D-5L - The EQ-5D-5L is a generic, self-administered preference-based measure of health. The five dimensions covered by the EQ-5D-5L include mobility, self-care, pain, usual activities, and anxiety/depression and is converted into a single summary index that can range from -0.594 to 1.0, with a score of 0 indicating death, 1.00 indicating "full health," and negative scores reflecting states perceived to be worse than death. Respondent's self-rated health on a vertical, 0 to 100 scale where 100 = "Best imaginable health state" and 0 = "Worst imaginable health state"

Time frame:
from the start of cycle 1 to cycle 7 day 1 approximately 170 days.
Reported as:
Mean · Scores on a Scale
Mean Change From Baseline in EQ-5D-5L Utility Index Score
Scores on a ScaleFedratinibBest Available Therapy (BAT)
C2D10.1086 ± 0.201880.0705 ± 0.22881
C3D10.1093 ± 0.239500.1142 ± 0.26247
C4D10.1214 ± 0.206340.0366 ± 0.26470
C5D10.1068 ± 0.213950.0321 ± 0.23607
C6D10.0594 ± 0.268640.0658 ± 0.24229
C7D10.0853 ± 0.240190.1066 ± 0.25848
SecondaryTime to Spleen and Disease Progression Free Survival (SDPFS)

Time from randomization to death due to any reason or disease progression (modified IWG-MRT 2013 including ≥ 25% increase in spleen volume by MRI/CT).

Time frame:
From randomization to the End of Survival Follow-up

Results for this outcome have not been posted.

SecondaryOverall Survival

Time from randomization to death due to any reason

Time frame:
From Randomization to the end of Survival Follow Up

Results for this outcome have not been posted.

Adverse events

Collected over Adverse Events, Serious Adverse Events and All Cause Mortality: From first dose to database lock: Approximately 3 years and 8 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fedratinib43/134 (32.1%)72/134 (53.7%)128/134 (95.5%)
Best Available Therapy (BAT)7/67 (10.4%)21/67 (31.3%)57/67 (85.1%)
Fedratinib After Crossover11/46 (23.9%)16/46 (34.8%)45/46 (97.8%)
Most frequent serious events
Showing 10 of 119
Most frequent serious events
EventFedratinibBest Available Therapy (BAT)Fedratinib After Crossover
General physical health deteriorationGeneral disorders10/1341/671/46
AnaemiaBlood and lymphatic system disorders9/1340/672/46
COVID-19Infections and infestations2/1343/673/46
Urinary tract infectionInfections and infestations1/1340/673/46
Acute kidney injuryRenal and urinary disorders7/1341/670/46
PneumoniaInfections and infestations3/1343/672/46
LeukocytosisBlood and lymphatic system disorders1/1342/670/46
Cardiac failureCardiac disorders4/1341/670/46
COVID-19 pneumoniaInfections and infestations1/1342/670/46
Atrial fibrillationCardiac disorders3/1340/670/46
Most frequent other events
Showing 10 of 47
Most frequent other events
EventFedratinibBest Available Therapy (BAT)Fedratinib After Crossover
DiarrhoeaGastrointestinal disorders62/1343/6717/46
AnaemiaBlood and lymphatic system disorders55/13424/6719/46
NauseaGastrointestinal disorders54/13410/6711/46
ThrombocytopeniaBlood and lymphatic system disorders48/13412/6713/46
ConstipationGastrointestinal disorders30/1346/676/46
AstheniaGeneral disorders27/13415/678/46
VomitingGastrointestinal disorders24/1343/679/46
COVID-19Infections and infestations19/1344/679/46
Oedema peripheralGeneral disorders25/1347/676/46
Night sweatsSkin and subcutaneous tissue disorders8/1349/677/46

Baseline characteristics

Intent to Treat population

Age, Continuous
Age, Continuous(Years)FedratinibBest Available Therapy (BAT)Total
Mean68.7 ± 8.7967.6 ± 8.1668.4 ± 8.58
Sex: Female, Male
Sex: Female, Male(Participants)FedratinibBest Available Therapy (BAT)Total
Female593796
Male7530105
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)FedratinibBest Available Therapy (BAT)Total
Hispanic or Latino8311
Not Hispanic or Latino10657163
Unknown or Not Reported20727
Race (NIH/OMB)
Race (NIH/OMB)(Participants)FedratinibBest Available Therapy (BAT)Total
American Indian or Alaska Native011
Asian9514
Native Hawaiian or Other Pacific Islander000
Black or African American000
White10658164
More than one race000
Unknown or Not Reported19322
08

Study locations

107 sites
  • Local Institution - 103
    Darlinghurst, New South Wales 2010, Australia
  • Local Institution - 101
    Adelaide, South Australia 5000, Australia
  • Local Institution - 105
    Box Hill, Victoria 3128, Australia
  • Local Institution - 102
    Langwarrin, Victoria 3910, Australia
  • Local Institution - 100
    Melbourne, 3004, Australia
  • Local Institution - 156
    Graz, 73013, Austria
  • Local Institution - 154
    Innsbruck, 6020, Austria
  • Local Institution - 155
    Linz, 4020, Austria
  • Local Institution - 151
    Salzburg, 5020, Austria
  • Local Institution - 150
    Vienna, 1090, Austria
  • Local Institution - 152
    Vienna, 1140, Austria
  • Local Institution - 153
    Wels, 4600, Austria
  • Local Institution - 200
    Bruges, 8000, Belgium
  • Local Institution - 202
    Brussels, 1200, Belgium
  • Local Institution - 205
    La Louvière-(Haine St-Paul), 7100, Belgium
  • Local Institution - 201
    Leuven, 3000, Belgium
  • Local Institution - 204
    Liège, 4000, Belgium
  • Local Institution - 203
    Yvoir, 5530, Belgium
  • Local Institution - 555
    Beijing, 100044, China
  • Local Institution - 550
    Guangzhou, Guangdong, 510080, China
  • Local Institution - 553
    Tianjin, 300041, China
  • Local Institution - 557
    Zhengzhou, 0, China
  • Local Institution - 700
    Brno, 625 00, Czechia
  • Local Institution - 702
    Ostrava-Poruba, 708 52, Czechia
  • Local Institution - 701
    Prague, 128 08, Czechia
  • Local Institution - 255
    Angers, 49033, France
  • Local Institution - 256
    Brest, 29200, France
  • Local Institution - 254
    Lens, 62307, France
  • Local Institution - 259
    Lille, 59037, France
  • Local Institution - 260
    Nice, 06200, France
  • Local Institution - 250
    Nîmes, 30029, France
  • Local Institution - 252
    Paris, 75010, France
  • Local Institution - 258
    Pessac, 33604, France
  • Local Institution - 257
    Pierre-Bénite, 69495, France
  • Local Institution - 261
    Poitiers, 86021, France
  • Local Institution - 251
    Strasbourg, 67091, France
  • Local Institution - 253
    Toulouse, 31059, France
  • Local Institution - 302
    Aachen, 52074, Germany
  • Local Institution - 308
    Frankfurt am Main, 60590, Germany
  • Local Institution - 306
    Halle, 06120, Germany
  • Local Institution - 303
    Jena, 07747, Germany
  • Local Institution - 307
    Magdeburg, 39120, Germany
  • Local Institution - 301
    Mannheim, 68167, Germany
  • Local Institution - 304
    Minden, 32429, Germany
  • Local Institution - 305
    Ulm, 89081, Germany
  • Local Institution - 600
    Budapest, 1088, Hungary
  • Local Institution - 601
    Győr, 9024, Hungary
  • Local Institution - 602
    Kaposvár, 7400, Hungary
  • Local Institution - 604
    Nyíregyháza, 4400, Hungary
  • Local Institution - 603
    Szeged, 6720, Hungary
  • Local Institution - 751
    Cork, T12 DFK4, Ireland
  • Local Institution - 752
    Dublin, Dublin 7, Ireland
  • Local Institution - 750
    Dublin, Dublin 8, Ireland
  • Local Institution - 353
    Bologna, 40138, Italy
  • Local Institution - 363
    Brescia, 25123, Italy
  • Local Institution - 354
    Catania, 95123, Italy
  • Local Institution - 350
    Florence, 50134, Italy
  • Local Institution - 358
    Milan, 20122, Italy
  • Local Institution - 362
    Naples, 80131, Italy
  • Local Institution - 357
    Pavia, 27100, Italy
  • Local Institution - 356
    Roma, 00168, Italy
  • Local Institution - 361
    Roma, 00168, Italy
  • Local Institution - 359
    Roma, 00189, Italy
  • Local Institution - 355
    Torino, 10126, Italy
  • Local Institution - 360
    Udine, 33100, Italy
  • Local Institution - 352
    Varese, 21100, Italy
  • Local Institution - 364
    Verona, 37134, Italy
  • Local Institution - 402
    Maastricht, 6229 HX, Netherlands
  • Local Institution - 400
    Nijmegen, 6525 GA, Netherlands
  • Local Institution - 803
    Poznan, 61-848, Poland
  • Local Institution - 801
    Warsaw, 02-776, Poland
  • Local Institution - 802
    Wroclaw, 50-556, Poland
  • Local Institution - 855
    Moscow, 125167, Russia
  • Local Institution - 851
    Moscow, 125284, Russia
  • Local Institution - 853
    Moscow, 129301, Russia
  • Local Institution - 857
    Novosibirsk, 630066, Russia
  • Local Institution - 852
    Saint Petersburg, 191024, Russia
  • Local Institution - 854
    Saint Petersburg, 197022, Russia
  • Local Institution - 850
    Saint Petersburg, 197341, Russia
  • Local Institution - 859
    Vladikavkaz, 362002, Russia
  • Local Institution - 900
    Seongnam-si, 13620, South Korea
  • Local Institution - 905
    Seoul, 06351, South Korea
  • Local Institution - 901
    Seoul, 06591, South Korea
  • Local Institution - 903
    Seoul, 140-887, South Korea
  • Local Institution - 904
    Seoul, 3080, South Korea
  • Local Institution - 902
    Seoul, 5505, South Korea
  • Local Institution - 451
    Alicante, 03010, Spain
  • Local Institution - 452
    Badalona (Barcelona), 8916, Spain
  • Local Institution - 458
    Barakaldo, 48903, Spain
  • Local Institution - 450
    Barcelona, 08036, Spain
  • Local Institution - 462
    Girona, 17007, Spain
  • Local Institution - 461
    Las Palmas de Gran Canaria, 35012, Spain
  • Local Institution - 453
    Madrid, 28034, Spain
  • Local Institution - 459
    Madrid, 28041, Spain
  • Local Institution - 457
    Málaga, 29010, Spain
  • Local Institution - 454
    Murcia, 30008, Spain
  • Local Institution - 455
    Salamanca, 37007, Spain
  • Local Institution - 463
    Santa Cruz de Tenerife, 38320, Spain
  • Local Institution - 460
    Santiago de Compostela, 15706, Spain
  • Local Institution - 456
    Valencia, 46010, Spain

Showing the first 100 of 107 sites across 16 countries.

09

References and documents

Publications

  • Harrison CN, Mesa R, Talpaz M, Al-Ali HK, Xicoy B, Passamonti F, Palandri F, Benevolo G, Vannucchi AM, Mediavilla C, Iurlo A, Kim I, Rose S, Brown P, Hernandez C, Wang J, Kiladjian JJ. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Haematol. 2024 Oct;11(10):e729-e740. doi: 10.1016/S2352-3026(24)00212-6. Epub 2024 Sep 9. PubMed 39265613 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 23, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 28, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03952039
Lead sponsor
Celgene
Collaborators
Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation
Responsible party
Sponsor
First posted
May 16, 2019
Start date
Sep 9, 2019
Primary completion
Dec 15, 2022
Completion
Jul 28, 2025
Results posted
Jan 30, 2024
Last update
Aug 28, 2025

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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